Macrophages induce T cell apoptosis in patients with advanced gastric cancer

In patients with tumors, down-regulation of T cell signaling is related to T cell apoptosis. Now, a team of Japanese researchers has found new clues to the relationship between macrophages in tumor-draining lymph nodes and T cell apoptosis in cancer patients.

In the May issue of the International Journal of Cancer, Dr. Akihiro Takahashi and colleagues at the Yamanashi Medical University describe experiments in which they co-cultured macrophages in tumor-draining lymph nodes with autologous peripheral blood T cells from patients with various stages of gastric cancer.In samples from patients with very early disease, rates of apoptosis were similar in the co-cultured T cells and in control T cells. In samples from patients with advanced disease, however, a significantly greater proportion of co-cultured T cells underwent apoptosis compared with control T cells. Apoptosis in the co-cultured T cells correlated with elevated caspase activity and followed impaired T cell function, according to the report.The authors note that “addition of a selective scavenger of [hydrogen peroxide] inhibited the apoptosis of T cells co-cultured with macrophages in tumor-draining lymph nodes in patients with advanced disease.”In addition, they note, the production of hydrogen peroxide was “significantly higher” in macrophages in tumor-draining lymph nodes from patients with advanced disease compared with macrophages from those with early disease. Furthermore, levels of interleukin-10 and interleukin-12 were higher in the macrophages in tumor-draining lymph nodes from patients with advanced disease.”This is the first study that demonstrates that macrophages in tumor-draining lymph nodes induce apoptosis of autologous T cells, concomitant to…elevated caspase activity and following impaired T-cell function,” the investigators state.In the future, they add, “normalization of T-cell function by antioxidant therapy or manipulation of tumor-associated macrophages should precede more specific immune interventions [such as] vaccination with defined tumor antigens and cytokine-induced activation of T cells.”(Source: Int J Cancer 2003; 104:393-399: Reuters Health: May 23, 2003: Oncolink)